One of the unique features of the H-2 complex, the major histocompability complex of mice, is the extensive polymorphism of its loci, that is, the occurrence in natural populations of a great number of alleles at the individual loci. The objective of this project is to determine the extent of the H-2 polymorphism, the nature of variation of the H-2 genes, the mechanisms involved in the establishment and maintenance of the polymorphism, and the relationship of the polymorphism to the function of the H-2 loci. To determine the extent of the polymorphism, H-2 homozygous mouse lines and H-2 heterozygous cell lines carrying H-2 haplotypes of wild mice will be established; monoclonal antibodies against allele-specific antigenic determinants of these lines will be produced; and wild mice will be typed with these reagents to determine the H-2 gene and haplotype frequencies in different populations. The new lines will also be used to elucidate in detail the genetic organization of the H-2 complex. The nature of H-2 variation will be established by biochemical methods based on comparative tryptic peptide mapping of H-2 molecules. The mechanisms of maintenance of the H-2 polymorphism will be probed by determining the temporal stability of H-2 gene frequencies, the ways new H-2 haplotypes can be introduced into an established population, and the influence of linked loci on the H-2 polymorphism. The biological function of the H-2 polymorphism will be tested by determining the effects selected intracellular parasites (viruses) have on the composition of H-2 alleles in a given population. Combined together, these approaches should bring us closer to an understanding of H-2 function and evolution. They may also shed light on the origins and migration of mouse populations and thus indirectly also on the origins and migration patterns of human populations. (CS)